2. Academic Validation
  3. Protective effect of resveratrol against colistin-induced nephrotoxicity through regulating Nrf2 pathway and inhibiting ferroptosis

Protective effect of resveratrol against colistin-induced nephrotoxicity through regulating Nrf2 pathway and inhibiting ferroptosis

  • Free Radic Biol Med. 2026 Apr:247:39-53. doi: 10.1016/j.freeradbiomed.2026.02.009.
Zhisheng Hu 1,  Weihua Hao 1,  Na Cui 1,  Xin Gao 1,  Wenqing Dai 1,  Minge Wang 2,  Liangxing Fang 1,  Jian Sun 1,  Hongyan Zhang 3,  Xiaoping Liao 4
Affiliations

Affiliations

  • 1 Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, PR China; Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, 510642, PR China; National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, 510642, PR China.
  • 2 Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, PR China; Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, 510642, PR China; National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, 510642, PR China; College of Agriculture and Biology, Liaocheng University, Liaocheng, Shandong, 252000, PR China.
  • 3 Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, PR China; Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, 510642, PR China; National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, 510642, PR China. Electronic address: [email protected].
  • 4 Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, PR China; Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, 510642, PR China; National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, 510642, PR China. Electronic address: [email protected].
PMID: 41654146 DOI: 10.1016/j.freeradbiomed.2026.02.009
Abstract

Resveratrol (Res), a natural polyphenol, is widely used as a functional food additive and food preservative due to its antioxidant and anti-inflammatory properties. However, its protective role against drug-induced organ damage, particularly colistin-induced nephrotoxicity (CIN), remains underexplored. This study investigated Res's protective effects and mechanisms against CIN in rat and NRK-52E cells. In vivo, Res (5-20 mg/kg) significantly improved renal function, alleviated histopathological damage, and restored antioxidant status. Mechanistically, Res modulated the Keap1/Nrf2 axis, suppressing excessive Nrf2 activation and its downstream Enzymes. Concurrently, Res inhibited Ferroptosis by reducing iron accumulation and modulating key Ferroptosis markers (GPX4, ACSL4). In vitro, Res (20 μM) reversed CS- and RSL3-induced cytotoxicity, lipid peroxidation, and ferrous iron overload; Nrf2 siRNA abrogated these effects, confirming Nrf2's essential role. These findings highlight Res as a promising strategy to enhance colistin's clinical safety through precise Nrf2 modulation and Ferroptosis inhibition, underscoring the therapeutic potential of natural food compounds.

Keywords

Colistin; Ferroptosis; Nephrotoxicity; Nrf2; Resveratrol.

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